β-Elemene induces apoptosis of human rheumatoid arthritis fibroblast-like synoviocytes via reactive oxygen species-dependent activation of p38 mitogen-activated protein kinase

• Published in: Pharmacological reports Vol. 68; no. 1; pp. 7 - 11
• Main Authors: Zou, Shibo, Wang, Changyin, Cui, Zhengjun, Guo, Pengfei, Meng, Qingnan, Shi, Xun, Gao, Ya, Yang, Gaoyuan, Han, Zhaofeng
• Format: Journal Article
• Language: English
• Published: Cham Elsevier Urban & Partner Sp. z o.o 01.02.2016; Springer International Publishing
• Subjects: Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Arthritis, Rheumatoid - enzymology; Arthritis, Rheumatoid - pathology; Cell Survival - drug effects; Cell Survival - physiology; Cells, Cultured; Dose-Response Relationship, Drug; Drug Safety and Pharmacovigilance; Enzyme Activation - drug effects; Enzyme Activation - physiology; Fibroblasts - drug effects; Fibroblasts - enzymology; Fibroblasts - pathology; Humans; Original Research Article; Oxidative stress; p38 Mitogen-Activated Protein Kinases - metabolism; Pharmacotherapy; Pharmacy; Reactive Oxygen Species - metabolism; Rheumatoid arthritis; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology; Synovial Membrane - drug effects; Synovial Membrane - enzymology; Synovial Membrane - pathology; β-Elemene; β-Elemene; Oxidative stress; Rheumatoid arthritis; Apoptosis
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/j.pharep.2015.06.004

β-Elemene is a natural anticancer compound extracted from the Chinese medicinal herb Curcuma Wenyujin. This study was done to determine the effect of β-elemene on the apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and associated molecular mechanisms. RA-FLS were treated for 72h with β-elemene at 10–200μg/ml and cell viability and apoptotic changes were examined. The involvement of reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) was checked. We found that β-elemene significantly inhibited the viability and promoted apoptosis of RA-FLS in a concentration-dependent fashion. β-Elemene-treated FLS showed a significant decline in mitochondrial membrane potential, an accumulation of cytochrome c in the cytosol, and increased activities of caspase-9 and caspase-3. β-Elemene treatment caused an enhancement of p38 MAPK phosphorylation and ROS production. The pro-apoptotic activity of β-elemene was significantly reversed by pretreatment with the p38 inhibitor SB203580 or ROS inhibitor N-acetyl-l-cysteine. Taken together, β-elemene is effective in inducing mitochondrial apoptosis of RA-FLS, which is mediated through induction of ROS formation and p38 MAPK activation. β-Elemene may thus have therapeutic benefits for RA.